Viruses of the family Herpesviridae, each having an overall size of approximately 150 nm to 200 nm, are such that a core protein is surrounded by multi-stranded DNA with molecular masses of 80 to 150×106 daltons. This multi-stranded DNA is enclosed in an icosahedral capsid which has a diameter of approximately 100 nm and is made of 162 capsomers, so as to form a nucleocapsid which is surrounded by an envelope. Herpes viruses have been found in almost all mammals and amphibians. In particular, viruses of the family Herpesviridae that have host specificity for humans are named human herpesviruses (HHVs). HHVs are classified into subfamilies Alphaherpesvirinae (e.g., herpes simplex virus and varicella-zoster herpes virus), Betaherpesvirinae (e.g., cytomegalovirus), and Gammaherpesvirinae (e.g. EB virus).
These herpes viruses are characterized by having a stage of latent infection. The “latent infection” refers to such a state of infection that a virus that has infected a host cell does not produce infectious virions within the host cell but continues to survive. Even in this phase of latent infection, virus genes and gene products that help the virus genes to exist are retained within the host cell. Herpes viruses that exhibit latent infection are known to resume production of virions and viral replication in a large amount owing to certain causes on the side of the host (e.g. growing old and somatic complaints (including fatigue)). This state is called “reactivation”.
In short, herpes viruses have the following unique character: Herpes viruses continue to infect the host latently as long as the host has nothing abnormal; however, once a somatic disturbance occurs in the host and the viruses detect that the host is in danger, the viruses are reactivated to seek another, healthy host.
To study the biology of such viruses of the family Herpesviridae, understanding their latent infection and reactivation is essential. However, among the many herpes viruses, it is only EB virus belonging to the subfamily Gammaherpesvirinae that has been studied to yield many findings about latent infection, and much remains unclear about other viruses.
In particular, concerning factors that may be involved in latent infection of Betaherpesvirinae, there has been obtained no information other than from the findings previously made by the present inventors. For example, Non-Patent Document 1 discloses latent infection of HHV-6 in macrophages in peripheral blood which macrophages have differentiated to a relatively high extent, and identifies the sites in a host at which sites the host is latently infected with HHV-6. Non-Patent Document 2 describes very frequent invasion of HHV-6 into a brain upon primary infection to cause persistent infection and latent infection. Non-Patent Document 3 discloses genes (latent infection genes) that are expressed during latent infection of HHV-6, and suggests that those genes play the role of regulating latent infection and reactivation of the virus.
Non-Patent Document 4 shows that the state of latent infection with HHV-6 involves an intermediate stage which is comparatively stable and allows for active gene expression, with the result that a latent infection gene and a protein (latent infection gene protein) encoded by this gene are expressed abundantly. What is more, Non-Patent Document 5 shows that patients with chronic fatigue syndrome had in their sera antibodies against latent infection gene proteins which are expressed at an increased level in the intermediate stage.
Non-Patent Document 1    Kondo. K et al. Latent human herpesvirus 6 infection of human monocytes/macrophages (J Gen Virol 72:1401-1408, 1991)
Non-Patent Document 2    Kondo. K et al. Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. (J Infect Dis 167:1197-1200, 1993.)
Non-Patent Document 3    Kondo. K et al. Identification of human herpesvirus 6 latency-associated transcripts. (J Virol. 76: 4145-4151, 2002)
Non-Patent Document 4    Kondo K et al. Recognition of a Novel Stage of Beta-Herpesvirus Latency in Human Herpesvirus 6. (J Virol. 77: 2258-2264, 2003)
Non-Patent Document 5    Kazuhiro Kondo, “Herpesvirus Kansen to Hiro (Herpesvirus latency and fatigue)”, Virus, 2005, Vol. 55, No. 1, pages 9 to 18